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기타논문
Date: 13 March 2022
Journal: Internation Journal of Molecular Sciences , Doi: https://doi.org/10.3390/ijms23063094
2022 | <b class="sch_word">The</b>rapeutic Effect of Melittin–dKLA Targeting Tumor-Associated Macrophages in Melanoma…
- Ik-Hwan Han 1,† , Chanmi Jeong 1,2, Juwon Yang 1,2, Seung-Hyeok Park 3 , Deok-Sang Hwang 3,* and Hyunsu Bae 1,*
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2022 IJMS-melanoma.pdf
(1.2M)Abstract: Melanoma is an immunogenic tumor and a serious type of skin cancer. Tumor-associated macrophages (TAMs) express an M2-like phenotype and are involved in all stages of melanomagenesis; it is hence a promising target for cancer immunotherapy. We herein investigated whether melittin–dKLA inhibits the growth of melanoma by inducing apoptosis of M2-like macrophages.
For the in vitro study, a conditioned medium of macrophages was prepared from M0, M1, or M2-differentiated THP-1 cells with and without melittin–dKLA. The affinity of melittin for M2 macrophages was studied with FITC (fluorescein isothiocyanate)-conjugated melittin. For the in vivo study, murine melanoma cells were inoculated subcutaneously in the right flank of mice, melittin–dKLA was intraperitoneally injected at 200 nmol/kg every three days, and flow cytometry analysis of TAMs was performed. Since melittin binds preferentially to M2-like macrophages, melittin–dKLA induced more caspase 3 expression and cell death in M2 macrophages compared with M0 and M1 macrophages and melanoma cells. Melittin–dKLA significantly inhibited the proliferation and migration of M2 macrophages, resulting in a decrease in melanoma tumor growth in vivo. The CD206+ M2-like TAMs were reduced, while the CD86+ M1-like TAMs were not affected. Melittin–dKLA is therapeutically effective against melanoma by inducing the apoptosis of M2-like TAMs.
Keywords: melanoma; melittin–dKLA; tumor-associated macrophage; M2 macrophage; therapeutic agent
